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Signals from the blood of the mother enhance the maturation of the brain

16.09.2008

Neuroscientists characterize the signalling chain

The maturation of the brain of unborn infants is given a gentle “prod” by its mother. A protein messenger from the mother’s blood is transferred to the embryo and stimulates the growth and wiring of the neurons in the brain.

Neuroscientists in Bochum (Prof. Petra Wahle, Developmental Neurobiology at the Ruhr University), Magdeburg (Dr. Peter Landgraf, Prof. Michael R. Kreutz) and in Münster (Prof. Hans-Christian Pape) performed a detailed investigation of this signal transduction pathway and identified those molecules in the brain of the embryo that interact with the maternal messenger. This achievement delivers an important step towards the comprehension of this signal transduction pathway. Their research work is published in the current volume of the Journal of Biological Chemistry.

In previous studies, the scientists had already managed to isolate the polypeptide messenger that plays a decisive role in the brain development of embryos and newborn infants, namely the “survival promoting peptide / Y P30.” Y-P30 enhances the survival of thalamic (diencephalic) neurons and promotes the neuritogenic activity of cerebellar and thalamic neurons. Prof. Wahle explained that it is “interesting to note that Y-P30 is not synthesized directly within the developing infant brain, but is produced by specific immune cells of the mother’s blood during pregnancy.

From there it passes the blood-placenta barrier and accumulates - inter alia - in neurons of the cerebral cortex of the embryo.” (Landgraf P, Sieg F, Wahle P, Meyer G, Kreutz MR, Pape HC (2005) “A maternal blood-borne factor promotes survival of the developing thalamus”. FASEB Journal 19:225-227.”) The scientists were able to provide evidence of the peptide in the brain of fetuses of mice and humans, and of postnatal rats.

Messengers need receptors to be effective

It was of particular interest to identify possible receptors for Y-P30 to enable investigation of the biological role of the messenger and to clarify its mechanisms of action. The research team has succeeded in identifying the molecules that interact with Y-P30, namely pleiotrophin, a protein within the extracellular space, and so-called syndecans, i.e. proteins on the cell surface. It was known that both binding partners could promote the growth of neurons. The scientists were now able to show the Y-P30 enhances the development of the pleiotrophin/syndecan signaling complex and stabilizes it.

The signaling activity within the neurons is increased and enhances the neuritogenic activity. Prof. Petra Wahle and Suvarna Wagh, PhD student in research training group 736, were able to demonstrate a direct action of the Y-P30 peptide on the growth of axons (neurites). The signal-receptor-complex comprised of Y-P30, pleiotrophin und syndecan thus appears to enhance the development of the axonal projection tracts and the wiring of the brain.

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